For a variety of reasons, thermoplastic elastomers are not used in the pharmaceutical industry in great quantities. Because of extremely high quality control and concern for the integrity of the product contained in pharmaceutical containers, thermoplastic elastomers have been slow to be accepted as candidates for container closures. Of particular concern are those pharmaceutical primary closures which need to provide a satisfactory barrier to moisture and oxygen and at the same time not allow undesirable materials to be extracted from the closure into the contents. The property of being able to withstand or maintain vacuum for long periods of time is important if container or its contents are stored for a long time.
One particular line of closures in the pharmaceutical industry which has a great but unsatisfied need for improvement are those closures which are used as blood tube stoppers. These products are particularly sensitive to contamination of the blood contained in the tube either by extraction from the container or closure, or from external contamination. Particularly of concern is the leakage of moisture and/or oxygen through the elastomeric closure to adversely affect the blood which is contained in the tube. At the same time, it is absolutely essential that the elastomeric closures function as a true stopper, being sufficiently elastomeric to conform to the shape of the tube, and being readily insertable into the tube. It is also essential that the closure be suitable for penetration by a needle when the contents are either added to or removed from the tube.
This particular need for appropriate closures in the pharmaceutical industry is not easily satisfied even by thermoset products. Some forms of butyl rubber in a thermoset formulation have been compounded which are suitable for use as blood tube stoppers. Butyl rubber products can be permanently crosslinked to form thermosetting compositions using curing systems which do not contaminate the product. Attempts to provide thermoplastic elastomers based upon butyl rubber formulations have, in part, been successful for some applications such as molded mechanical goods and the like. However, these formulations have been uniformly unsuitable for use in the pharmaceutical industry.
For example, U.S. Pat. No. 4,130,534 describes a thermoplastic composition containing polyolefin resins and crosslinked butyl rubber. The product is formed by dynamic vulcanization, in which the rubber is the continuous phase prior to crosslinking but becomes the dispersed phase after the crosslinking step. These products are used for tires, hoses, belts, gaskets and the like.
In U.S. Pat. No. 4,504,842, an adhesive using halogenated butyl rubber combined with block thermoplastic polymers is described in which zinc oxide is used to increase the strength of the product. Zinc oxide, it should be noted, it particularly undesirable in pharmaceutical applications due to the adverse affects of zinc ions as a contaminant.
Dynamic vulcanization itself is extensively described in U.S. Pat. No. 4,593,062. This patent is directed to molded parts for automobile hoses and external body parts. In another patent which describes dynamic vulcanization, the second rubber, preferably EPDM, is employed with the zinc oxide cure system as shown in U.S. Pat. No. 4,607,074. Again, gaskets, seals and the like are described as the end products.
U.S. Pat. No. 4,616,064 is one of very few patents which describe the use of thermoplastic materials in the medical field. This patent describes a mixture of polyolefins, SEBS polymers and materials such as polysiloxanes. These materials are suggested to be useful as tubing, particularly when in contact with human skin. These elastomers are incapable of providing a barrier to moisture and oxygen. Furthermore, they would be non-functional as primary closures for pharmaceutical containers.
Finally, U.S. Pat. No. 4,616,052 discloses high temperature creep resistant thermoplastic elastomer compositions which may be used in a variety of medical applications. The primary advantage described by this patent is the ability to withstand temperatures such as those encountered during autoclaving. The principal components of the product are dynamically vulcanized ethylene-propylene-diene terpolymer and polypropylene. The composition also includes a small amount of butyl rubber in the range of about 5 to about 20 percent.
None of the system described above is capable of providing a suitable composition for use in the pharmaceutical industry. Accordingly, it is an object of this invention to provide a thermoplastic elastomer composition which is useful as a molded primary closure for the pharmaceutical industry. This product should be suitable for use in combination with a pharmaceutical tube as a stopper. The object of this invention is to provide a composition which has properties which protect pharmaceutical products which are contained in an appropriate container. More particularly, it is an object of this invention to provide an improved blood tube stopper for use in the pharmaceutical industry.